Genetic Variant ZNF467:c.-176G>C (chr7-149776369-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000882861.1(ZNF467):c.-176G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000763 in 1,363,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

ZNF467
ENST00000882861.1 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.304

Publications

1 publications found

Variant links:

Genes affected

ZNF467 (HGNC:23154): (zinc finger protein 467) The protein encoded by this gene is a zinc finger protein whose function has not yet been elucidated in humans. However, the mouse ortholog of this protein enhances adipocyte differentiation and suppresses osteoblast differentiation in bone marrow. The mouse protein also is a transcription factor for several genes and can help recruit histone deacetylase complexes. [provided by RefSeq, Aug 2016]

ZNF467 links:

SSPOP (HGNC:21998): (SCO-spondin, pseudogene) Predicted to enable peptidase inhibitor activity. Predicted to be involved in several processes, including cell adhesion; negative regulation of catalytic activity; and regulation of peptidase activity. Predicted to be located in cytoplasm. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SSPOP links:

ENSG00000293556 (HGNC:):

ENSG00000293556 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0051960945).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000882861.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSPOP	NR_163594.1		n.74C>G		non_coding_transcript_exon	Exon 2 of 103

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
ZNF467	ENST00000882861.1	c.-176G>C	5_prime_UTR	Exon 1 of 5	ENSP00000552920.1
ZNF467	ENST00000882862.1	c.-440G>C	5_prime_UTR	Exon 1 of 7	ENSP00000552921.1
ZNF467	ENST00000882863.1	c.-552G>C	5_prime_UTR	Exon 1 of 7	ENSP00000552922.1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000187

AC:

AN:

240046

AF XY:

0.000161

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000590

Gnomad ASJ exome

AF:

0.00419

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000342

GnomAD4 exome

AF:

0.0000718

AC:

AN:

1211414

Hom.:

Cov.:

AF XY:

0.0000717

AC XY:

AN XY:

599926

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26266

American (AMR)

AF:

0.0000541

AC:

AN:

36972

Ashkenazi Jewish (ASJ)

AF:

0.00352

AC:

AN:

16784

East Asian (EAS)

AF:

0.00

AC:

AN:

16720

South Asian (SAS)

AF:

0.00

AC:

AN:

82418

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4430

European-Non Finnish (NFE)

AF:

0.0000168

AC:

AN:

952692

Other (OTH)

AF:

0.000228

AC:

AN:

43848

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000112

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000273

Hom.:

Bravo

AF:

0.000128

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000706

AC:

ExAC

AF:

0.0000995

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.38

CADD

Benign

5.4

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.040

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0052

MutationAssessor

Uncertain

2.0

PhyloP100

-0.30

PrimateAI

Benign

0.40

Sift4G

Benign

0.11

Polyphen

0.011

Vest4

0.21

MVP

0.13

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.029

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over